PMID- 36646010 OWN - NLM STAT- MEDLINE DCOM- 20230206 LR - 20230206 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 251 DP - 2023 Feb TI - Taraxasterol alleviates aflatoxin B(1)-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy. PG - 114546 LID - S0147-6513(23)00050-7 [pii] LID - 10.1016/j.ecoenv.2023.114546 [doi] AB - Aflatoxin B(1) (AFB(1)) is the most dangerous and abundant mycotoxin, which is toxic to almost all animals, and poultry is more sensitive to AFB(1) toxicity. Ingesting AFB(1)-contaminated feed can cause significant liver damage and brings serious harm to poultry, which greatly restricts the development of the poultry industry. The present research was implemented to explore the intervention effect and its mechanism of taraxasterol on liver damage induced by AFB(1) in broiler chickens. The liver damage model in broiler chickens was established by feeding 0.5 mg/kg AFB(1) feed, and taraxasterol (25, 50 and 100 mg/kg BW, respectively) was given in the drinking water for 21 days. The growth performance, liver function, oxidative stress, apoptosis and autophagy were evaluated. The results showed that taraxasterol increased BW and reduced feed-to-gain ratio of broiler chickens induced by AFB(1). Taraxasterol improved the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBIL) and alkaline phosphatase (ALP), and attenuated hepatic histopathological changes induced by AFB(1). Meantime, taraxasterol down-regulated cytochrome P450 (CYP450) enzyme system CYP1A1 and CYP2A6 mRNA expression, inhibited the overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and enhanced the activities of antioxidant enzymes glutathione (GSH) and catalase (CAT) and the content of antioxidant superoxide dismutase (SOD) of the liver in broiler chickens induced by AFB(1). Furthermore, taraxasterol up-regulated the mRNA and protein expression of hepatic nuclear factor E2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and down-regulated the expression of hepatic kelch like ECH associated protein 1 (Keap1) induced by AFB(1) in Keap1/Nrf2 signaling pathway. The ultrastructural observation and RT-qPCR results found that taraxasterol inhibited apoptosis of hepatocytes, up-regulated the expression of B-cell lymphoma-2 (Bcl-2) mRNA and down-regulated the expression of Bax and caspase3 mRNA. Further, taraxasterol restored the autophagy of hepatocytes and down-regulated the mRNA expression of phosphatidylinositol 3-kinase K (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in AFB(1)-induced liver of broiler chickens. The above results indicate that taraxasterol alleviates liver damage induced by AFB(1) in broiler chickens through regulation of Keap1/Nrf2 signaling pathway to exert its antioxidant effect, mitochondrial apoptosis pathway to improve anti-apoptotic ability and PI3K/AKT/mTOR pathway to restore autophagy. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Sang, Rui AU - Sang R AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: 1017585240@qq.com. FAU - Ge, Bingjie AU - Ge B AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: 727965819@qq.com. FAU - Li, Haifeng AU - Li H AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: Lihaifeng@ybu.edu.cn. FAU - Zhou, Hongyuan AU - Zhou H AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: 840242579@qq.com. FAU - Yan, Kexin AU - Yan K AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: 411517796@qq.com. FAU - Wang, Wei AU - Wang W AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: 1255360108@qq.com. FAU - Cui, Qichao AU - Cui Q AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: 1132679802@qq.com. FAU - Zhang, Xuemei AU - Zhang X AD - Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: zhangxm@ybu.edu.cn. LA - eng PT - Journal Article DEP - 20230114 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Antioxidants) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 9N2N2Y55MH (Aflatoxin B1) RN - 64SK2ERN9P (taraxasterol) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (NF-E2-Related Factor 2) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - GAN16C9B8O (Glutathione) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - *Antioxidants/metabolism MH - *Proto-Oncogene Proteins c-akt/metabolism MH - Chickens/metabolism MH - Aflatoxin B1/toxicity MH - Kelch-Like ECH-Associated Protein 1/metabolism MH - NF-E2-Related Factor 2/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Oxidative Stress MH - Liver MH - Apoptosis MH - Glutathione/metabolism MH - TOR Serine-Threonine Kinases/genetics/metabolism MH - RNA, Messenger/metabolism MH - Autophagy MH - Mammals/metabolism OTO - NOTNLM OT - Aflatoxin B(1) OT - Broiler chickens OT - Liver damage OT - Oxidative stress OT - Taraxasterol COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/01/17 06:00 MHDA- 2023/02/07 06:00 CRDT- 2023/01/16 18:08 PHST- 2022/10/31 00:00 [received] PHST- 2022/12/22 00:00 [revised] PHST- 2023/01/11 00:00 [accepted] PHST- 2023/01/17 06:00 [pubmed] PHST- 2023/02/07 06:00 [medline] PHST- 2023/01/16 18:08 [entrez] AID - S0147-6513(23)00050-7 [pii] AID - 10.1016/j.ecoenv.2023.114546 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2023 Feb;251:114546. doi: 10.1016/j.ecoenv.2023.114546. Epub 2023 Jan 14.